An anticancer agent is the general term for the drugs that directly interact with DNA of cancer cell to interrupt replication, transcription and translation at the cancer cells or intervene between the metabolism pathway to interrupt the synthesis of nucleic acid precursor and to inhibit cancer cell division to bring anticancer effect which means toxicity against cancer cells. The anticancer agent is a kind of proliferation-dependent drug which works for active proliferating cells only. So, the anticancer agent can be classified as the antiproliferative drug. Especially, cell cycle arrest and apoptosis are the two most important mechanisms of an anticancer agent for its cytotoxicity or antiproliferative activity. Therefore, the induction of cell cycle arrest and/or apoptosis is the major target for the development of an anticancer agent.
Cell cycle is composed of four phases which are G1, S, G2 and M. G1 phase is the period for the synthesis of proteins necessary for cell growth, specifically enzymes and structural proteins for cell division. S phase is the period for synthesis of intracellular DNA. G2 phase is the period for the preparation of mitosis. And M phase is the period for cell division including nuclear division and cytokinesis. When G1 phase is unnecessarily extended so that cell division is suspended, it is called G0 phase. In general, the whole cell division period depends on the length of G1 phase. Cancer cells are constantly proliferated and the period of G0/G1 phase of cancer cells is shorter than that of normal cells, suggesting that their cell division is very fast. So, it is one way to inhibit cancer cell growth separately from normal cells to treat a drug that is able to arrest cell cycle in a specific phase which is repeated fast in the case of cancer cells.
Daurinol, an arylnaphthalene lignan, is a single chemical component, which was first isolated from Haplophyllum dauricum, the medicinal plant of Mongolia, by the present inventors in early 1980s. The daurinol was also isolated from Haplophyllum cappadocicum, same family but a different plant. However, its pharmacological activity has never been reported yet. Haplophyllum sp. plants are perennial grasses and widely spread in central Asia. They have been used for the traditional folk remedy for various diseases over hundreds of years.
The present inventors completed this invention by confirming that daurinol isolated from the Mongolian medicinal plant Haplophyllum dauricum could arrest cell cycle of cancer cells selectively at S phase, induce apoptosis and reveal the cell toxicity stepwise and therefore it can be effectively used for the production of a novel cell cycle blocker, a novel apoptosis inducer, a novel cytotoxic agent, a pharmaceutical composition for the prevention and treatment of cancer.